Self‐reactive forbidden clones are confined to pathways of intermediate T‐cell receptor cell differentiation even under immunosuppressive conditions

Moroda, Tetsuya; Kawachi, Yasuyuki; Iiai, Tsuneo; Tsukahara, Akihiro; Suzuki, Susumu; Tada, Takashi; Watanabe, Hirotaka; Hatakeyama, Katsuyoshi; Abo, Toru

doi:10.1046/j.1365-2567.1997.00222.x

Cited by 28 publications

(29 citation statements)

References 28 publications

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“…Primarily, extrathymic T cells have autoreactivity because of their limited negative selection 25–27 . Among these extrathymic T cells, CD8 + NK1·1 − TCR int cells have an allorecognition ability 20 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of extrathymic CD8αβ T cells in the liver and intestine in TAP‐1 deficient mice

Tsukada¹,

Miyaji²,

Kawamura³

et al. 2003

Immunology

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SUMMARYTAP-1 de®cient (À/À) mice cannot transport MHC class I antigens onto the cell surface, which results in failure of the generation of CD8T cells in the thymus. In a series of recent studies, it has been proposed that extrathymic T cells are generated in the liver and at other extrathymic sites (e.g. the intestine). It was therefore investigated whether CD8 extrathymic T cells require an interaction with MHC class I antigens for their differentiation in TAP-1(À/À) mice. Although CD8 thymically derived T cells were con®rmed to be absent in the spleen as well as in the thymus, CD8abT cells were abundant in the livers and intestines of TAP-1(À/À) mice. These CD8 T cells expanded in the liver as a function of age and were mainly con®ned to a NK1Á1 À CD3 int population which is known to be truly of extrathymic origin. Hepatic lymphocytes, which contained CD8 T cells and which were isolated from TAP-1(À/À) mice (H-2 b ), responded to neither mutated MHC class I antigens (bm1) nor allogeneic MHC class I antigens (H-2 d ) in in vitro mixed lymphocyte cultures. However, the results from repeated in vivo stimulations with alloantigens (H-2 d ) were interesting. Allogeneic cytotoxicity was induced in liver lymphocytes in TAP-1(À/À) mice, although the magnitude of cytotoxicity was lower than that of liver lymphocytes in immunized B6 mice. All allogeneic cytotoxicity disappeared with the elimination of CD8 cells in TAP-1(À/À) mice. These results suggest that the generation and function of CD8 extrathymic T cells are independent of the existence of the MHC class I antigens of the mouse but have a limited allorecognition ability.

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Section: Discussionmentioning

confidence: 99%

Characterization of extrathymic CD8αβ T cells in the liver and intestine in TAP‐1 deficient mice

Tsukada¹,

Miyaji²,

Kawamura³

et al. 2003

Immunology

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“…We previously showed the distinct functional properties of extrathymic T cells and thymus-derived T cells. Namely, extrathymic T cells (TCR int cells) eliminate abnormal self-cells (mainly self-antigens in the context of monomorphic major histocompatibility complex antigen) because of their autoreactivity (i.e., innate immunity), [21][22][23][24] whereas thymus-derived T cells (TCR high cells) interact with foreign antigens (mainly in the FIG. 7.…”

Section: Discussionmentioning

confidence: 99%

Consistent infiltration of thymus-derived T cells into the parenchymal space of the liver in normal mice

et al. 1999

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We previously reported that extrathymic T cells (intermediate T-cell receptor cells [TCRIn a series of recent studies, 1-4 we have shown that the adult liver is one of the hematopoietic organs in mice, mainly producing extrathymic T cells (i.e., interleukin-2 receptor ␤ chain (IL-2R␤) ϩ intermediate T-cell receptor cells [TCR int cells]) and granulocytes from their own pre-existing precursor cells (i.e., c-kit ϩ Lin Ϫ stem cells). On the other hand, the bone marrow produces all hematopoietic cells, whereas the intestine (i.e., its cryptopatches) produces only extrathymic T cells. 5,6 Reflecting the above-mentioned situation, we have often encountered clusters of lymphoid and myeloid cells in the parenchymal space of the liver in normal or estrogentreated mice. 3 Because such clusters always contain c-kit ϩ Lin Ϫ cells and dividing cells (bromodeoxyuridine ϩ cells), 3,7 it is presumed that these clusters might be sites for the generation of extrathymic T cells and granulocytes in the liver. A similar phenomenon (i.e., c-kit ϩ Lin Ϫ cells giving rise to extrathymic T cells) occurs in the cryptopatches of the small intestine. 5,6 In the course of these studies, we observed that some lymphocytes also exist dispersely in the parenchymal space of the liver (including Glisson' s area) without cluster formation, even in normal adult mice. To determine the origin of these lymphocytes (namely, their being of extrathymic origin or of thymic origin), we intensively characterized the phenotype of cells before and after liver irrigation. Although intensive liver irrigation with physiological saline from the portal vein enriched extrathymic T cells (i.e., TCR int cells), thymus-

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“…In addition, it has been shown that chronic stress caused by immobilisation affects the number of lymphocytes in rats, but impacts on different subsets in different ways (Dominguez-Gerpe and Rey-Mendez 2001). The overall decrease in the number of circulating lymphocytes was accompanied by the increase in the number of mainly immature T lymphocytes, suggesting one of the potential mechanisms by which stress-associated immunosuppression can affect and exacerbate autoimmune diseases (Moroda et al 1997).…”

Section: Stress and The Immune Systemmentioning

confidence: 99%

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

Vitlić

Lord

Phillips

2014

AGE

100

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The immune response is essential for keeping an organism healthy and for defending it from different types of pathogens. It is a complex system that consists of a large number of components performing different functions. The adequate and controlled interaction between these components is necessary for a robust and strong immune response. There are, however, many factors that interfere with the way the immune response functions. Stress and ageing now consistently appear in the literature as factors that act upon the immune system in the way that is often damaging. This review focuses on the role of stress and ageing in altering the robustness of the immune response first separately, and then simultaneously, discussing the effects that emerge from their interplay. The special focus is on the psychological stress and the impact that it has at different levels, from the whole system to the individual molecules, resulting in consequences for physical health.

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Self‐reactive forbidden clones are confined to pathways of intermediate T‐cell receptor cell differentiation even under immunosuppressive conditions

Cited by 28 publications

References 28 publications

Characterization of extrathymic CD8αβ T cells in the liver and intestine in TAP‐1 deficient mice

Characterization of extrathymic CD8αβ T cells in the liver and intestine in TAP‐1 deficient mice

Consistent infiltration of thymus-derived T cells into the parenchymal space of the liver in normal mice

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

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